tbuckley/cabot-search huggingface dataset:
Results of salvage therapy with mini-hyper-CVD and inotuzumab ozogamicin with or without blinatumomab in pre-B acute lymphoblastic leukemia
Authors: Hagop Kantarjian, Fadi G. Haddad, Nitin Jain, Koji Sasaki, Nicholas J. Short, Sanam Loghavi, Rashmi Kanagal-Shamanna, Jeffrey Jorgensen, Issa Khouri, Partow Kebriaei, Yesid Alvarado, Tapan Kadia, Shilpa Paul, Guillermo Garcia-Manero, Bouthaina Dabaja, Musa Yilmaz, Jovitta Jacob, Rebecca Garris, Susan O’Brien, Farhad Ravandi, Elias Jabbour
Journal: Journal of Hematology & Oncology (2023)

Abstract Background Historically, adults with relapsed-refractory acute lymphoblastic leukemia (ALL) experienced poor outcomes with intensive chemotherapy. This mature analysis explores the benefit of the addition of sequential blinatumomab to low-intensity mini-Hyper-CVD chemotherapy with inotuzumab ozogamicin in this setting. Methods Mini-Hyper-CVD (cyclophosphamide and dexamethasone at 50% dose reduction, no anthracycline, methotrexate at 75% dose reduction, cytarabine at 83% dose reduction) was combined with inotuzumab during the first 4 courses. From Patient #68 and onwards, inotuzumab was given in reduced and fractionated doses, and blinatumomab was added sequentially for 4 courses. Maintenance therapy with prednisone, vincristine, 6-mercaptopurine and methotrexate was given for 12 courses, and blinatumomab for 4 additional courses. Results Among 110 patients (median age, 37 years) treated, 91 (83%) responded (complete response, 69 patients, 63%). Measurable residual disease negativity was documented in 75 patients (82% of responders). Fifty-three patients (48%) received allogeneic stem cell transplantation (SCT). Hepatic sinusoidal obstruction syndrome occurred in 9/67 patients (13%) on the original inotuzumab schedule and in 1/43 (2%) on the modified schedule. With a median follow-up of 48 months, the median overall survival (OS) was 17 months, and the 3 year OS was 40%. The 3 year OS was 34% with mini-Hyper-CVD plus inotuzumab and 52% with additional blinatumomab ( P = 0.16). By landmark analysis at 4 months, the 3 year OS was 54%, similar between patients who did or did not receive allogeneic SCT. Conclusion Low-intensity mini-Hyper-CVD plus inotuzumab with or without blinatumomab showed efficacy in patients with relapsed-refractory ALL, with better survival after the addition of blinatumomab. Trial registration The trial was registered on clinicaltrials.gov with the identifier NCT01371630.
Racial and Ethnic Bias in the Diagnosis of Alcohol Use Disorder in Veterans
Authors: Rachel Vickers-Smith, Amy C. Justice, William C. Becker, Christopher T. Rentsch, Brenda Curtis, Anita Fernander, Emily E. Hartwell, Eseosa T. Ighodaro, Rachel L. Kember, Janet Tate, Henry R. Kranzler
Journal: American Journal of Psychiatry (2023)

Studies show that racially and ethnically minoritized veterans have a higher prevalence of alcohol use disorder (AUD) than White veterans. The investigators examined whether the relationship between self-reported race and ethnicity and AUD diagnosis remains after adjusting for alcohol consumption, and if so, whether it varies by self-reported alcohol consumption.
Facile Synthesis of Highly Stretchable, Tough, and Photodegradable Hydrogels
Authors: Rita G. Fonseca, Aline Kuster, Pedro P. Fernandes, Mahmoud Tavakoli, Patrícia Pereira, José R. Fernandes, Francesco De Bon, Arménio C. Serra, Ana C. Fonseca, Jorge F. J. Coelho
Journal: Advanced Healthcare Materials (2023)

Abstract Recently, highly stretchable and tough hydrogels that are photodegradable on‐demand have been reported. Unfortunately, the preparation procedure is complex due to the hydrophobic nature of the photocrosslinkers. Herein, a simple method is reported to prepare photodegradable double‐network (DN) hydrogels that exhibit high stretchability, toughness, and biocompatibility. Hydrophilic ortho ‐nitrobenzyl (ONB) crosslinkers incorporating different poly(ethylene glycol) (PEG) backbones (600, 1000, and 2000 g mol −1 ) are synthesized. These photodegradable DN hydrogels are prepared by the irreversible crosslinking of chains by using such ONB crosslinkers, and the reversible ionic crosslinking between sodium alginate and divalent cations (Ca 2+ ). Remarkable mechanical properties are obtained by combining ionic and covalent crosslinking and their synergistic effect, and by reducing the length of the PEG backbone. The rapid on‐demand degradation of these hydrogels is also demonstrated by using cytocompatible light wavelength ( λ = 365 nm) that degrades the photosensitive ONB units. The authors have successfully used these hydrogels as skin‐worn sensors for monitoring human respiration and physical activities. A combination of excellent mechanical properties, facile fabrication, and on‐demand degradation holds promise for their application as the next generation of substrates or active sensors eco‐friendly for bioelectronics, biosensors, wearable computing, and stretchable electronics.
Pregnancy Intention, Changes in Pregnancy Intention, and Pregnancy Incidence Among Female Nurses in North America
Authors: Siwen Wang, Lidia Minguez-Alarcon, Melissa Perez Capotosto, Makiko Mitsunami, Audrey J. Gaskins, Brittany M. Charlton, Jaime E. Hart, Janet W. Rich-Edwards, Jorge E. Chavarro
Journal: JAMA Network Open (2023)

Importance Pregnancy intention assessment is a key element of preconception and contraceptive care. The association between a single screening question and the incidence of pregnancy is unknown. Objective To prospectively evaluate the dynamics of pregnancy intention and pregnancy incidence. Design, Setting, and Participants This prospective cohort study (the Nurses’ Health Study 3) was conducted from June 1, 2010, to April 1, 2022, in 18 376 premenopausal, nonpregnant female nurses aged 19 to 44 years. Main Outcomes and Measures Pregnancy intention and pregnancy status were assessed at baseline and approximately every 3 to 6 months thereafter. Cox proportional hazards regression models were used to estimate the association between pregnancy intention and pregnancy incidence. Results A total of 18 376 premenopausal, nonpregnant women (mean [SD] age, 32.4 [6.5] years) participated in the study. At baseline, 1008 women (5.5%) were trying to conceive, 2452 (13.3%) were contemplating pregnancy within 1 year, and the remaining 14 916 (81.2%) were neither trying to conceive nor thought they would be pregnant within 1 year. A total of 1314 pregnancies were documented within 12 months of pregnancy intention assessment. The cumulative incidence of pregnancy was 38.8% in women actively trying to conceive (median [IQR] time to pregnancy, 3.3 [1.5-6.7] months), 27.6% in women contemplating pregnancy (median [IQR] time to pregnancy, 6.7 [4.2-9.3] months), and 1.7% in women neither trying to conceive nor contemplating pregnancy (median [IQR] time to pregnancy, 7.8 [5.2-10.5] months) among those who became pregnant. Women who were actively trying to conceive were 23.1 times (95% CI, 19.5-27.4 times) and women who were contemplating pregnancy were 13.0 times (95% CI, 11.1-15.2 times) more likely to conceive within 12 months than women who were neither attempting nor contemplating pregnancy. Among women contemplating pregnancy at baseline who did not get pregnant during follow up, 18.8% were actively trying and 27.6% were not trying by 12 months. Conversely, only 4.9% of women neither trying to conceive nor contemplating pregnancy within 1 year at baseline changed pregnancy intention during follow up. Conclusions and Relevance In this cohort study of reproductive-aged nurses in North America, pregnancy intention was highly fluid among women who were contemplating pregnancy but relatively stable among women trying to conceive and women who were neither trying to conceive nor contemplating pregnancy. Pregnancy intention was strongly associated with pregnancy incidence, but the median time to pregnancy points to a relatively short time window to initiate preconception care.
A centre-based ambulatory care concept for hidradenitis suppurativa improves disease activity, disease burden and patient satisfaction: results from the randomized controlled EsmAiL trial
Authors: Michael Schultheis, Petra Staubach, Georgios Nikolakis, Lukas Schollenberger, Melanie  Mauch, Marion Burckhardt, Marcus Heise, Marina Zamsheva, Alexandra  Strobel, Gero Langer, Falk Bechara, Uwe Kirschner, Katharina Hennig, Christian Kunte, Matthias Goebeler, Stephan Grabbe
Journal: British Journal of Dermatology (2023)

Hidradenitis suppurativa (HS) is an inflammatory disease of the inverse skin regions that occurs in young women, in particular, and affects approximately 1% of the population. Outpatient care is often inadequate and usually cannot prevent progression.To evaluate in the EsmAiL ('Evaluation eines strukturierten und leitlinienbasierten multmodalen Versorgungskonzepts für Menschen mit Akne inversa') trial whether an innovative care concept can decrease disease activity and burden, and improve patient satisfaction.EsmAiL was conducted as a two-arm, multicentre, prospective, randomized controlled trial that included 553 adults with HS. Inclusion criteria were a minimum of three inflammatory lesions and at least a moderate impact of the disease on quality of life. The control group (CG) remained under standard care, while patients in the intervention group (IG) were treated according to a trial-specific, multimodal concept. The primary endpoint was the absolute change in International Hidradenitis Suppurativa Severity Score System (IHS4).In total, 274 patients were randomized to the IG and 279 to the CG. Altogether, 377 attended the final assessment after 12 months of intervention. Participants in the IG (n = 203) achieved a mean improvement in IHS4 of 9.3 points, while the average decrease in IHS4 in patients in the CG (n = 174) was 5.7 points (P = 0.003). Patients treated under the new care concept also reported a statistically significantly higher decrease in pain, Dermatology Life Quality Index and Hospital Anxiety and Depression Scale scores compared with those in the CG (P < 0.001). Patient satisfaction was also statistically significantly higher in the IG compared with the CG (P < 0.001).The establishment of standardized treatment algorithms in so-called 'acne inversa centres' in the ambulatory setting has a substantial, positive impact on the course of HS and significantly improves patient satisfaction.
SARS-CoV-2 infection and recovery in children: Distinct T cell responses in MIS-C compared to COVID-19
Authors: Ksenia Rybkina, Joseph N. Bell, Marissa C. Bradley, Teddy Wohlbold, Marika Scafuro, Wenzhao Meng, Rebecca C. Korenberg, Julia Davis-Porada, Brett R. Anderson, Rachel J. Weller, Joshua D. Milner, Anne Moscona, Matteo Porotto, Eline T. Luning Prak, Kalpana Pethe, Thomas J. Connors, Donna L. Farber
Journal: The Journal of Experimental Medicine (2023)

SARS-CoV-2 infection for most children results in mild or minimal symptoms, though in rare cases severe disease can develop, including a multisystem inflammatory syndrome (MIS-C) with myocarditis. Here, we present longitudinal profiling of immune responses during acute disease and following recovery in children who developed MIS-C, relative to children who experienced more typical symptoms of COVID-19. T cells in acute MIS-C exhibited transient signatures of activation, inflammation, and tissue residency which correlated with cardiac disease severity, while T cells in acute COVID-19 upregulated markers of follicular helper T cells for promoting antibody production. The resultant memory immune response in recovery showed increased frequencies of virus-specific memory T cells with pro-inflammatory functions in children with prior MIS-C compared to COVID-19 while both cohorts generated comparable antibody responses. Together our results reveal distinct effector and memory T cell responses in pediatric SARS-CoV-2 infection delineated by clinical syndrome, and a potential role for tissue-derived T cells in the immune pathology of systemic disease.
The risk of venous thromboembolism increases within one month of gout flare: comment on the article by Cipolletta et al
Authors: Gang Wang, Ning Zhuo, Zhichun Liu
Journal: Arthritis & Rheumatology (2023)

Disclosure Form Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Diagnostic Accuracy of Unenhanced Computed Tomography for Evaluation of Acute Abdominal Pain in the Emergency Department
Authors: Hiram Shaish, Justin Ream, Chenchan Huang, Jonathan Troost, Sonia Gaur, Ryan Chung, Sooah Kim, Hanisha Patel, Jeffrey H. Newhouse, Shokoufeh Khalatbari, Matthew S. Davenport
Journal: JAMA Surgery (2023)

Intravenous (IV) contrast medium is sometimes withheld due to risk of complication or lack of availability in patients undergoing computed tomography (CT) for abdominal pain. The risk from withholding contrast medium is understudied.
Author Correction: Unique progerin C-terminal peptide ameliorates Hutchinson–Gilford progeria syndrome phenotype by rescuing BUBR1
Authors: Na Zhang, Qianying Hu, Tingting Sui, Lu Fu, Xinglin Zhang, Yu Wang, Xiaojuan Zhu, Baiqu Huang, Jun Lu, Zhanjun Li, Yu Zhang
Journal: Nature Aging (2023)
Errors in Results, Discussion, Table 1, and the Supplement
Journal: JAMA Network Open (2023)

Rose L. Molina, MD, MPH; Thomas C. Tsai, MD, MPH; Dannie Dai, BS; Mark Soto, MA; Ning Rosenthal, MD, MPH, PhD; E. John Orav, PhD; Jose F. Figueroa, MD, MPH
Location and condition based reconstruction of colon cancer microbiome from human RNA sequencing data
Authors: Gaia Sambruni, Angeli D. Macandog, Jakob Wirbel, Danilo Cagnina, Carlotta Catozzi, Tiziano Dallavilla, Francesca Borgo, Nicola Fazio, Uberto Fumagalli-Romario, Wanda L. Petz, Teresa Manzo, Simona P. Ravenda, Georg Zeller, Luigi Nezi, Martin H. Schaefer
Journal: Genome Medicine (2023)

Abstract Background The association between microbes and cancer has been reported repeatedly; however, it is not clear if molecular tumour properties are connected to specific microbial colonisation patterns. This is due mainly to the current technical and analytical strategy limitations to characterise tumour-associated bacteria. Methods Here, we propose an approach to detect bacterial signals in human RNA sequencing data and associate them with the clinical and molecular properties of the tumours. The method was tested on public datasets from The Cancer Genome Atlas, and its accuracy was assessed on a new cohort of colorectal cancer patients. Results Our analysis shows that intratumoural microbiome composition is correlated with survival, anatomic location, microsatellite instability, consensus molecular subtype and immune cell infiltration in colon tumours. In particular, we find Faecalibacterium prausnitzii , Coprococcus comes , Bacteroides spp., Fusobacterium spp. and Clostridium spp. to be strongly associated with tumour properties. Conclusions We implemented an approach to concurrently analyse clinical and molecular properties of the tumour as well as the composition of the associated microbiome. Our results may improve patient stratification and pave the path for mechanistic studies on microbiota-tumour crosstalk.
Crohn’s disease proteolytic microbiota enhances inflammation through PAR2 pathway in gnotobiotic mice
Authors: Alba Santiago, Amber Hann, Marco Constante, Sara Rahmani, Josie Libertucci, Kyle Jackson, Gaston Rueda, Laura Rossi, Rithwik Ramachandran, Wolfram Ruf, Jon Schertzer, Alberto Caminero, Premysl Bercik, Heather Jean Galipeau, Elena Francisca Verdu
Journal: Gut Microbes (2023)

Emerging evidence implicates microbial proteolytic activity in ulcerative colitis (UC), but whether it also plays a role in Crohn's disease (CD) remains unclear. We investigated the effects of colonizing adult and neonatal germ-free C57BL/6 mice with CD microbiota, selected based on high (CD-HPA) or low fecal proteolytic activity (CD-LPA), or microbiota from healthy controls with LPA (HC-LPA) or HPA (HC-HPA). We then investigated colitogenic mechanisms in gnotobiotic C57BL/6, and in mice with impaired Nucleotide-binding Oligomerization Domain-2 (NOD2) and Protease-Activated Receptor 2 (PAR2) cleavage resistant mice (Nod2−/−; R38E-PAR2 respectively). At sacrifice, total fecal proteolytic, elastolytic, and mucolytic activity were analyzed. Microbial community and predicted function were assessed by 16S rRNA gene sequencing and PICRUSt2. Immune function and colonic injury were investigated by inflammatory gene expression (NanoString) and histology. Colonization with HC-LPA or CD-LPA lowered baseline fecal proteolytic activity in germ-free mice, which was paralleled by lower acute inflammatory cell infiltrate. CD-HPA further increased proteolytic activity compared with germ-free mice. CD-HPA mice had lower alpha diversity, distinct microbial profiles and higher fecal proteolytic activity compared with CD-LPA. C57BL/6 and Nod2−/− mice, but not R38E-PAR2, colonized with CD-HPA had higher colitis severity than those colonized with CD-LPA. Our results indicate that CD proteolytic microbiota is proinflammatory, increasing colitis severity through a PAR2 pathway.
Multiple Erythematous-Violaceous Patches and Plaques on the Left Upper Arm and Left Side of the Chest
Authors: Tian Chen, Dong-Lai Ma
Journal: JAMA Dermatology (2023)

A woman in her late 20s had multiple, slowly growing, infiltrated erythematous-violaceous patches and plaques with occasional slight pain extending from her left upper arm to the left side of her chest. What is your diagnosis?
Commentary on: Hemihepatic versus total hepatic inflow occlusion for laparoscopic hepatectomy: a randomized controlled trial
Authors: Bingqiang Ma, Ruohuang Si
Journal: International Journal of Surgery (2023)

Department of General Surgery, Gansu Provincial Hospital, Lanzhou 730000, Gansu, China Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article. Published online ■ ■ *Corresponding author. Address: CHINA. E-mail address: [email protected] (R. Si). This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0/
Combination Therapy, Including Bevacizumab, for Advanced Colorectal Cancer
Authors: Oladapo O. Yeku, Dan L. Longo
Journal: New England Journal of Medicine (2023)

This editorial describes the science behind a clinical trial performed by Prager and colleagues: a test of trifluridine–tipiracil and bevacizumab to treat patients with refractory metastatic colorectal cancer.
Nondisordered Cannabis Use Among US Adolescents
Authors: Ryan S. Sultan, Alexander W. Zhang, Mark Olfson, Muhire H. Kwizera, Frances R. Levin
Journal: JAMA Network Open (2023)

Importance Cannabis use is increasingly viewed by adolescents as not harmful. Youths with cannabis use disorder (CUD) are recognized by clinicians as being at risk for adverse outcomes, yet little is known about the associations between subclinical cannabis use (ie, nondisordered cannabis use [NDCU]) and adverse psychosocial events. Objective To describe the prevalence and demographics of NDCU and to compare associations of cannabis use with adverse psychosocial events among adolescents with no cannabis use, NDCU, and CUD. Design, Setting, and Participants This cross-sectional study used a nationally representative sample derived from the 2015 to 2019 National Survey on Drug Use and Health. Participants were adolescents aged 12 to 17 years, separated into 3 distinct groups: nonuse (no recent cannabis use), NDCU (recent cannabis use below diagnostic threshold), and CUD. Analysis was conducted from January to May 2022. Exposures CUD, NDCU, or cannabis nonuse. NDCU was defined as endorsing recent cannabis use but not meeting the Diagnostic and Statistical Manual of Mental Disorders ( Fifth Edition ) ( DSM-5 ) CUD criteria. CUD was defined using DSM-5 criteria. Main Outcomes and Measures The main outcomes were prevalence of adolescents meeting criteria for NDCU and associations between adverse psychosocial events and NDCU, adjusted for sociodemographic characteristics. Results The 68 263 respondents (mean [SD] age, 14.5 [1.7] years; 34 773 [50.9%] males) included in the analysis represented an estimated yearly mean of 25 million US adolescents during 2015 to 2019. Among respondents, 1675 adolescents (2.5%) had CUD, 6971 adolescents (10.2%) had NDCU, and 59 617 adolescents (87.3%) reported nonuse. Compared with nonusers, individuals with NDCU had approximately 2 to 4 times greater odds of all adverse psychosocial events examined, including major depression (adjusted odds ratio [aOR], 1.86; 95% CI, 1.67-2.08), suicidal ideation (aOR, 2.08; 95% CI, 1.88-2.29), slower thoughts (aOR, 1.76; 95% CI, 1.58-1.96), difficulty concentrating (aOR, 1.81; 95% CI, 1.65-2.00), truancy (aOR, 1.90; 95% CI, 1.67-2.16), low grade point average (aOR, 1.80; 95% CI, 1.62-2.00), arrest (aOR, 4.15; 95% CI, 3.17-5.43), fighting (aOR, 2.04; 95% CI, 1.80-2.31), and aggression (aOR, 2.16; 95% CI, 1.79-2.62). Prevalence of adverse psychosocial events was greatest for adolescents with CUD (range, 12.6% to 41.9%), followed by NDCU (range, 5.2% to 30.4%), then nonuse (range, 0.8% to 17.3%). Conclusions and Relevance In this cross-sectional study of US adolescents, past-year NDCU was approximately 4 times as prevalent as past-year CUD. A stepwise gradient association was observed for odds of adverse psychosocial events between adolescent NDCU and CUD. In the context of US normalization of cannabis use, prospective research into NDCU is necessary.
Incidence and cost of vertebral fracture in urban China: A five-year population-based cohort study
Authors: Xuan-Qi Zheng, Lu Xu, Jie Huang, Cheng-Gui Zhang, Wan-Qiong Yuan, Chui-Guo Sun, Zhi-Shan Zhang, Chen Wei, Jin-xi Wang, Steven R Cummings, Wei-Bo Xia, Sheng-Feng Wang, Si-Yan Zhan, Chun-Li Song
Journal: International Journal of Surgery (2023)

Background: Osteoporotic vertebral fractures cause pain and disability, which result in heavy socioeconomic burden. However, the incidence and cost of vertebral fractures in China are unknown. We aimed to assess the incidence and cost of clinically recognized vertebral fractures among people aged 50 years and older in China from 2013 to 2017. Materials and Methods: This population-based cohort study was conducted by using Urban Employee Basic Medical Insurance (UEBMI) and Urban Resident Basic Medical Insurance (URBMI) data in China from 2013 to 2017, which covered more than 95% of the Chinese population in urban areas. Vertebral fractures were identified by the primary diagnosis (i.e., International Classification of Diseases code or text of diagnosis) in UEBMI and URBMI. The incidence and medical cost of these clinically recognized vertebral fractures in urban China were calculated. Results: A total of 271,981 vertebral fractures (186,428, 68.5% females and 85,553, 31.5% males) were identified, with a mean age of 70.26 years. The incidence of vertebral fractures among patients aged 50 years and over in China increased approximately 1.79-fold during the five years, from 85.21 per 100,000 person-years in 2013 to 152.13 per 100,000 person-years in 2017. Medical costs for vertebral fracture increased from US$92.74 million in 2013 to US$505.3 million in 2017. Annual costs per vertebral fracture case increased from US$3.54 thousand in 2013 to US$5.35 thousand in 2017. Conclusion: The dramatic increase in the incidence and cost of clinically recognized vertebral fracture among patients aged 50 and over in urban China implies that more attention should be given to the management of osteoporosis to prevent osteoporotic fractures.